In many fluid processing systems involving filtration, there is a requirement to achieve the highest possible assurance of filter integrity and removal efficiency. Examples of such applications include sterilization of parenterals, biological liquids, and fluids used in fermentation processes. Conventional methods utilized to verify the integrity of porous filter media include: microbiological challenge tests, effluent cleanliness tests, particle challenge tests, forward flow tests (including pressure decay tests), and reverse bubble tests. The microbiological challenge, particle challenge and effluent cleanliness tests are destructive tests, and cannot be performed in a production environment. The industry-accepted non-destructive tests used to verify the integrity of porous elements are the forward flow test or the reverse bubble test. Both of these tests are performed by applying a predetermined gas pressure to a wetted filter.
Reverse bubble testing has been utilized since the 1950s to determine the size and location of the largest pore in a filter element. See, for example, D. B. Pall (U.S. Pat. No. 3,007,334, filed Nov. 30, 1956). A reverse bubble test (sometimes referred to as a first bubble test) detects defects by looking for bubbles while a wetted filter is submersed in a liquid. With the filter wetted and liquid covering one side of the filter, a gas at constant and/or variable pressure is directed against the other side of the filter.
At a certain pressure, the gas is just able to force the liquid from some of the largest pores in a filter having a homogenous pore structure, and the gas forms bubbles in the liquid covering the filter. This pressure is known as the bubble point of the filter. Of course, as the pressure increases above the bubble point, more and more of the liquid is forced from increasingly smaller pores of the filter and the flow of gas through the filter increases.
The bubble point of the filter depends on many factors, but pore size is a dominant factor. Filters having larger pores have a bubble point that occurs at lower pressures when using the same type of wetting solution. If the pressure of the gas is below the bubble point of the filter, very little gas passes through the filter. However, if there are defects in the filter, the gas will pass through the defects in the filter and bubbles will form in the liquid.
Bubbles rising in the liquid can be detected either visually or electronically using a passive sonar device which monitors a sudden increase in the sound intensity caused by bubbles rising and/or collapsing in the liquid. A device which ultrasonically detects a sudden increase in the sound intensity at the bubble point as bubbles rise/collapse in the liquid is, for example, shown by Reichelt, U.S. Pat. No. 4,744,240. Reichelt is utilized for determining the bubble point pressure of the largest pores in a homogeneous, non-defective filter. Reichelt is directed to determining the pressure at which a sudden increase in sound volume resulting from an applied pressure at a level in which gas is forced through a plurality of pores in a in-tact filter element having a relatively homogenous pore structure. The apparatus disclosed in Reichelt does not detect defective filters having pin-hole defects. Another problem with the apparatus disclosed in Reichelt is that the liquid media in which the ultrasonic transducer is disposed couples the microphone to sounds down stream of the filter element and throughout the fluid flow system. In this configuration, noise produced by bubbles from, for example, pin-holes becomes lost in the ambient noise of the system and sources of noise outside of the system. Additionally, the Reichelt device only detects a sudden rise in the noise level produced at the bubble point. It was found that many defective filters cannot be detected simply by measuring the sudden rise in the noise level.
Reverse bubble testing has a number of limitations. For filters having a cylindrical configuration, the filter must be rotated as it is observed for the formations of bubbles. The observation of bubbles is hindered by the fact that bubbles may be trapped by the filter as it is placed in the liquid, particularly where the filter has closely spaced pleats. Additionally, depending on the geometry of the filter, type of wetting solution, and the applied pressure, diffusional flow may produce several bubbles per second. Trapped bubbles and the bubbles from diffusional flow may provide a false indication that the filter is defective.
Reverse bubble testing is not well suited for testing a high volume of filters because the test takes a significant amount of time to complete and is subject to observer limitations. Further, it is exceedingly difficult and of limited value to simultaneously conduct a bubble test and a forward flow test. Additionally, it is impractical to reverse bubble test a filter in two different directions because of the limitations of the test apparatus and the filter construction (e.g., cartridge filters). Reverse bubble testing of a filter in an operational environment (on-line testing) is extremely difficult, and impractical under most circumstances. In addition to the above disadvantages, reverse bubble testing does not provide a quantitative assessment of the filter.
As a result of the limitations of reverse bubble tests, in the early 1970's Pall Corporation developed a filtration test known as the forward flow test. See, for example, Dr. D. B. Pall, 1973, "Quality Control of Absolute Bacteria Removal Filters", Parenteral Drug Association, Nov. 2, 1973. Conventional forward flow tests detect defects in a filter by measuring gas flow through a wetted filter. The forward flow test quantitatively measures the sum of diffusive flow and flow through any pores larger than a predetermined size.
In forward flow testing, the filter is typically placed in a test housing. The filter is wetted by immersing the filter in a liquid, such as water or alcohol, until all of the pores of the filter are filled with the liquid. The filter may be wetted by, for example, directing deionized water through the filter for a predetermined period of time. A gas is then directed under pressure against one side of the filter and gas flow through the wetted filter is measured by a flow meter, such as a mass flow meter.
If the filter has no defects, the gas at low pressures is unable to force the liquid from the pores of the filter, so there is very little gas flow, and typically only diffusive gas flow, through the filter. The wetted filter medium behaves like a sheet of wetting solution whose thickness is equal to that of the filter medium. The gas dissolves in the wetting solution, diffuses through it, and then is released downstream of the filter. At lower pressures, the flow per unit of applied pressure remains substantially constant. The flow measured at the lower pressures can be calculated for a given liquid from the known diffusion constant of the applied gas through the liquid.
At a certain higher pressure, known as the bubble point, the gas is just able to force the liquid from some of the largest pores in the filter, and a sudden increase in the flow of gas through the filter can be detected. Of course, as the pressure increases above the bubble point, more and more of the liquid is forced from the pores of the filter and the flow of gas through the filter increases. The slope of the curve after reaching the bubble point provides a measure of the uniformity of the pore sizes in the filter element. A more accurate measure of the "bubble point", is the quantity "K.sub.L ", coined from the term Knee Location, used to indicate the pressure at which the mass flow curve in a forward flow test bends.
Although the forward flow test is extensively used and is very reliable, it nonetheless has certain drawbacks. For example, the test takes a significant amount of time to complete. A large amount of time is required for gas flow to stabilize before testing can even begin. Once the test does begin, it must be conducted over an extended period of time in order to accurately measure the very small flow rates associated with modern filtration devices. Additionally, there may be a loss of accuracy for on-line testing using forward flow when several dozen filters are tested in parallel without isolating the individual flows through each of the parallel connected filter elements.